Graspa (eryaspase) / PHAXIAM Therap - LARVOL DELTA

TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma. (PubMed, J Clin Oncol) - P3 | "The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR. AEs were generally consistent with previous reports of chemotherapy. These results do not support additional development of eryaspase in PDAC."

Journal • P3 data • Hematological Disorders • Neutropenia • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Georgetown University | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Mar 2024

Trial completion • Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Efficient Implementation of Monte Carlo Algorithms on Graphical Processing Units for Simulation of Adsorption in Porous Materials. (PubMed, J Chem Theory Comput) - "The code is written in CUDA/C++ and SYCL/C++ to support different GPU vendors. The gRASPA code is publicly available at https://github.com/snurr-group/gRASPA."

Journal

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Georgetown University | Trial completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Metastases • Trial completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Georgetown University | Trial completion date: Dec 2024 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Dec 2022

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A phase I dose escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma. (ASCO 2023) - P1 | "The novel combination of mFOLFIRINOX plus eryaspase was well tolerated with no DLT and demonstrated signals of clinical activity in select patients. The MTD was declared with 5-FU 2400 mg/2, Oxaliplatin 85 mg/2, Irinotecan 150 mg/m2, and eryaspase 100 units/kg. Although the phase III Trybeca-1 trial did not meet the primary OS endpoint, both trials may suggest enhanced activity of eryaspase with regimens containing 5-Fluorouracil and Irinotecan."

Combination therapy • Metastases • P1 data • Anemia • Atrial Fibrillation • Cardiovascular • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Hypotension • Infectious Disease • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Septic Shock

Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441). (ASCO-GI 2019) - P2, P3; "Patients are randomized in a 1:1 ratio to receive gemcitabine/abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. An HR in OS of 0.725 is being targeted representing a conservative estimate based on the P2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals and to review efficacy data at the planned interim and final analyses."

Clinical • Combination therapy • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

A phase IIb of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180). (ASCO 2017) - P2; "This is the largest set of PC pts tested for the expression of ASNS and treated in second line with an asparaginase combined with chemotherapy. The ASNS expression levels may be a potential therapeutic target and therefore predictive of response to eryaspase for the treatment of advanced PC."

Biomarker • Clinical • Combination therapy • P2 data • Biosimilar • Ophthalmology • Pancreatic Cancer

A Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180) (ESMO 2017) - P2; "In pts with PC receiving second-line chemotherapy treatment, the addition of eryaspase provided significant improvement in OS and PFS, irrespective of ASNS expression levels. The role of the ASNS expression will be further investigated. Further investigation of eryaspase in PC in a P3 study is warranted."

Biomarker • Clinical • Combination therapy • P2 data • Pancreatic Cancer

Second-line treatment options for patients with metastatic pancreatic ductal adenocarcinoma: A systematic literature review. (PubMed, Cancer Treat Rev) - "The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue."

Journal • Metastases • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Expanded Access Program: Evaluating Safety of Erythrocytes Encapsulating L-Asparaginase in Combination with Polychemotherapy in Patients Under 55 Years Old with Acute Lymphoblastic Leukaemia (ALL) at Risk to Receive Other Formulations of Asparaginase (ASH 2021) - "All patients achieved target asparaginase activity. Therefore, eryaspase provides an additional option for patients for whom further ASNase treatment is contraindicated due to toxicity and/or immunization."

Clinical • Combination therapy • Acute Lymphocytic Leukemia • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology

A phase I dose-escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma: Interim update. (ASCO-GI 2022) - P1, P3 | "A second line pivotal randomized phase III trial (Trybeca-1), which compares chemotherapy (Gemcitabine + Nab-Paclitaxel or 5-Fluorouracil + Irinotecan) with or without Eryaspase, has completed enrollment with results pending (NCT03665441)... The novel combination of mFOLFIRINOX plus Eryaspase was well tolerated with no DLT and has encouraging signs of clinical activity. The MTD has been declared with 5-FU 2400 mg/2, Oxaliplatin 85 mg/2, Irinotecan 150 mg/m2, and Eryaspase 100 units/kg. We plan to expand enrollment to further look at efficacy and are in the process of designing a larger randomized study in the first line setting pending results from the Trybeca-1 trial."

Combination therapy • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with advanced pancreatic adenocarcinoma (NCT03665441). (ASCO-GI 2022) - P3 | "Patients were randomized in a 1:1 ratio to gemcitabine/nab-paclitaxel or irinotecan/fluorouracil (5FU) therapy (depending on first-line received) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. This large prospective study did not meet it primary endpoint of improving OS in patients treated with eryaspase. The addition of eryaspase demonstrated nevertheless a well-tolerated profile and an encouraging survival benefit in the irinotecan/5FU subgroup, warranting further investigation."

Clinical • Combination therapy • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Trybeca-1: Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC (clinicaltrials.gov) - P3 | N=512 | Completed | Sponsor: ERYtech Pharma | Active, not recruiting ➔ Completed | Trial completion date: Oct 2021 ➔ Jan 2022

Combination therapy • Trial completion • Trial completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

ERYTECH Provides Business and Financial Update for the First Half of 2022 (GlobeNewswire) - P2/3 | N=27 | TRYbeCA-2 (NCT03674242) | Sponsor: ERYtech Pharma | "Results of patients enrolled in TRYbeCA-2, Phase 2 clinical trial in triple-negative breast cancer (TNBC), reviewed: A total of 27 patients,11 and 14 evaluable patients in the eryaspase and control arms, respectively, have been finally enrolled. The trial’s Steering Committee met in September 2022 to review the results of the 25 evaluable patients. No clinical benefit was demonstrated, which could be attributed to the immature closure of the trial and the small number of patients. The treatment was well tolerated."

P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ERYTECH Provides Regulatory Update (GlobeNewswire) - "ERYTECH Pharma...provided a regulatory update, announcing that it is no longer seeking approval for Graspa® in hypersensitive acute lymphoblastic leukemia (ALL) following feedback from the U.S. Food and Drug Administration (FDA)....'The changing competitive landscape, combined with new FDA’s requests for additional clinical data that would require significant additional resources on our part, led to the difficult decision to stop the development of Graspa in ALL'."

Discontinued • FDA event • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Georgetown University | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2022 ➔ May 2023

Combination therapy • Enrollment closed • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone for the Treatment of TNBC (TRYbeCA-2) (clinicaltrials.gov) - P2/3 | N=27 | Terminated | Sponsor: ERYtech Pharma | N=64 ➔ 27 | Recruiting ➔ Terminated; sponsor decision

Combination therapy • Enrollment change • Trial termination • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process. (PubMed, Acta Pharm Sin B) - "Several parameters were compared between processed RBCs loaded with l-asparaginase ("eryaspase"), processed RBCs without drug and non-processed RBCs...Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms. Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function."

Journal

ERYTECH Sells U.S. Manufacturing Facility and Enters Long-Term Supply Agreement with Catalent (GlobeNewswire) - "ERYTECH Pharma...announced the sale of its U.S. manufacturing facility to Catalent, a leading contract development and manufacturing organization (CDMO) in advanced therapies....Under the terms of an asset purchase agreement between ERYTECH and Catalent (the 'APA'), Catalent agreed to acquire ERYTECH’s state-of-the-art commercial-scale cell therapy manufacturing facility in Princeton, New Jersey, for a total consideration of $44.5 million. ERYTECH’s current staff at the site of approximately 40 people will be offered Catalent’s employment....The parties will also enter into a long-term supply agreement, under which Catalent will manufacture ERYTECH’s lead product candidate eryaspase (GRASPA®) for clinical and commercial supply in the United States....ERYTECH has a Phase 1 trial in first-line pancreatic cancer ongoing in the United States...FDA regarding a potential BLA submission for GRASPA® in hypersensititve ALL, now targeted in the third quarter of 2022,..."

BLA • M&A • Acute Lymphocytic Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Solid Tumor

ERYTECH Announces Publication of Positive Results from Eryaspase Phase 2 Trial in Hypersensitive ALL in the British Journal of Haematology (GlobeNewswire) - P2 | N=55 | NOR-GRASPALL-2016 (NCT03267030) | "Eryaspase demonstrated sustained asparaginase enzyme activity above the threshold of >100 U/L at trough levels 14 days after first infusion in 92.5% of patients. Eryaspase was generally well tolerated when added to chemotherapy and almost all patients were able to receive the intended courses of asparaginase (median of 5 doses per patient). Of the 55 patients, only 2 patients had severe allergic reaction and withdrew eryaspase treatment."

P2 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Asparaginase encapsulated in erythrocytes as second-line treatment in hypersensitive patients with acute lymphoblastic leukaemia. (PubMed, Br J Haematol) - P2 | "Eryaspase was well tolerated, and most patients had AEA levels above the therapeutic target after the first infusion. The half-life of eryaspase confirmed that a 2-week schedule is appropriate."

Journal • Acute Lymphocytic Leukemia • Allergy • Hematological Malignancies • Immunology • Leukemia • Oncology

ERYTECH Provides Business and Financial Update for the Fourth Quarter and Full Year 2021 (GlobeNewswire) - "Key News Flow and Milestones Expected Over the Next 12 Months: (i) Planned BLA submission of eryaspase in hypersensitive ALL (Q2 2022); (ii) Data from the randomized Phase 2 TRYbeCA-2 trial of eryaspase in TNBC (Q3 2022); (iii) Results from the Phase 1 rESPECT Trial of eryaspase in combination with mFOLFIRINOX in first-line pancreatic cancer (2H 2022)."

BLA • P1 data • P2 data • Acute Lymphocytic Leukemia • Breast Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer

ERYTECH Announces Presentation of Results of Two Clinical Trials of Eryaspase in Pancreatic Cancer at ASCO GI (GlobeNewswire) - P3, N=500; Trybeca-1 (NCT03665441); Sponsor: ERYtech Pharma; "Full results from the TRYbeCA-1 Phase 3 trial of eryaspase in second-line metastatic pancreatic cancer, presented as a late-breaking oral presentation...The prespecified subgroup of patients treated with eryaspase and FOLFIRI, a fluoropyrimidine- and irinotecan-based chemotherapy regimen, demonstrated a nominal increase in median OS of 2.3 months versus FOLFIRI alone, from 5.7 to 8 months (HR = 0.81; 95% CI, 0.6-1.1)...'The Company intends to submit the BLA in the first quarter of 2022, subject to completion of remaining data requested by the FDA.'"

BLA • P3 data • Acute Lymphocytic Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

ERYTECH Announces Presentation of Results of Two Clinical Trials of Eryaspase in Pancreatic Cancer at ASCO GI (GlobeNewswire) - P1, N=18; NCT04292743; "ERYTECH Pharma...announced the presentation of results of two trials evaluating eryaspase in advanced pancreatic cancer at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) on January 21, 2022...The novel combination of mFOLFIRINOX plus eryaspase was well tolerated and no dose limiting toxicity (DLT) was observed. The maximum tolerated dose (MTD) has been declared with 5-FU 2400 mg/m2, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 and eryaspase 100 units/kg. Among ten patients with imaging available to evaluate response, 5 (50%) had partial response (PR) and 5 (50%) had stable disease (SD), corresponding to a disease control rate (PR + SD) of 100%...'We plan to expand enrolment on rESPECT to further evaluate efficacy.'"

Enrollment status • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma